Abstract

Water homeostasis is one of the body's most critical tasks. Physical challenges to the body, including exercise and surgery, almost always coordinate with some change in water handling reflecting the changing needs of the body. Vasopressin is the most important hormone that contributes to short-term water homeostasis. By manipulating vascular tone and regulating water reabsorption in the collecting duct of the kidneys, vasopressin can mediate the retention or loss of fluids quickly. In this study, we validated HumMod, an integrative mathematical model of human physiology, against six different challenges to water homeostasis with special attention to the secretion of vasopressin and maintenance of electrolyte balance. The studies chosen were performed in normal men and women, and represent a broad spectrum of perturbations. HumMod successfully replicated the experimental results, remaining within 1 standard deviation of the experimental means in 138 of 161 measurements. Only three measurements lay outside of the second standard deviation. Observations were made on serum osmolarity, serum vasopressin concentration, serum sodium concentration, urine osmolarity, serum protein concentration, hematocrit, and cumulative water intake following dehydration. This validation suggests that HumMod can be used to understand water homeostasis under a variety of conditions.

Protocols B–F began with a dehydration period. The effects of dehydration on serum AVP and osmolarity were reported at the beginning and end of dehydration, and are here compared to the simulated results from HumMod. Protocols C and D were statistically equivalent during dehydration, as were Protocols E and F, so we show only Protocols B,C, and F for clarity. Dashed lines represent simulations, whereas solid lines represent experimental data.

The water restriction protocols (Protocols B, C, and D) are shown along with their responses to rehydration. Serum osmolarity, AVP, and protein were measured in all three protocols and are shown for comparative purposes. Dashed lines represent simulations, whereas solid lines represent experimental data.

We show AVP, sodium, and hematocrit in the experimental and simulated response to hypertonic saline infusion, followed by either ad libidum water or no water (Protocols E and F). Dashed lines represent simulations, whereas solid lines represent experimental data. The gray bar in Panel A shows the water intake period.